|
|
|
|
|
|
|
|
|
|
|||||||
 |
 |
 |
||||||||||||||||
|
Advanced Ovarian CancerBy Sunni Hosemann Introduction Ovarian neoplasms comprise several pathologic subtypes. Epithelial ovarian cancers are the most common and cause the most deaths among patients with gynecologic cancers. The standard treatment of epithelial ovarian cancer is surgery and chemotherapy. Traditionally, surgery is done first, and chemotherapy is given postoperatively (adjuvantly). However, some patients benefit from receiving chemotherapy prior to surgery (neoadjuvant chemotherapy). Usually, patients who receive neoadjuvant chemotherapy also receive adjuvant chemotherapy, but this approach does not necessarily involve more treatment; rather than receive a course of six chemotherapy cycles after surgery, a patient might receive three before surgery and three after surgery. This article discusses the treatment alternatives for epithelial ovarian cancer, including factors to consider in deciding whether to give chemotherapy first, how many cycles to give, and when to perform surgery. No simple treatment plan for ovarian cancer exists, and the decisions in developing a personalized plan require careful evaluation, monitoring, and collaboration among specialists. Understanding Ovarian Cancer What gynecologic oncologists see when they look into the abdomen of a patient with ovarian cancer is not just a diseased ovary. A hallmark of ovarian cancer is abundant fluid manifesting as abdominal ascites and pleural effusion; whether this fluid is produced by the cancer itself or by the distressed organs is unknown. Presumably, the fluid is the vector of another curious behavior of ovarian cancer: the tendency of the tumor to spread by depositing cancer cells throughout the abdomen rather than by invading adjacent tissues before metastasizing via lymph and blood to distant locations. Ovarian cancer appears to initially “fall away” from the primary tumor into the fluid and then adhere to the surfaces of organs and membranes it contacts. Small surface tumors develop, appearing to have been “sprayed” onto the uterus, bladder, bowel, diaphragm, mesentery, liver, omentum—in fact, no abdominal organ or surface is immune. Later, the cancer can also spread via lymph and blood as many other cancers do. The surgery for ovarian cancer is therefore a major and extensive operation that includes a thorough exploration and possible resection of multiple organs. Every surface of every tissue in the abdomen must be examined for cancer. At M. D. Anderson, surgery for ovarian cancer is always led by gynecologic oncologists who have training and expertise in performing complex procedures. Initial Evaluation Patients who are seen by a gynecologic oncologist for the treatment of ovarian cancer have usually been referred after the discovery during physical examination of an abnormal pelvic mass, which is often confirmed by imaging (ultrasonography or computed tomography [CT]). It is also common for the disease to have been discovered during a surgical procedure, in which case there are usually tissue samples. “When ovarian cancer patients come to us, they may have had one of a number of procedures, including a CT scan, open biopsy, paracentesis, and thoracentesis, to make the diagnosis,” said Charles F. Levenback, M.D., professor and deputy chairman of M. D. Anderson’s Department of Gynecologic Oncology and clinical medical director of the Gynecologic Oncology Center. Histologic confirmation is not needed for a referral to M. D. Anderson, however. In fact, according to Kathleen M. Schmeler, M.D., an assistant professor in Gynecologic Oncology, it is preferable for the patient to be seen prior to any invasive procedure. That is not always possible, since ovarian cancer is sometimes discovered during an unrelated abdominal surgery. By the time the patient is seen by an oncologist for treatment, she may be suffering from a range of symptoms—from vague “bloating” and loss of appetite to considerable abdominal distention, pleural effusion, and frank malnutrition. Patients are often depressed as well, according to Dr. Levenback. Treatment As stated earlier, the standard treatment for ovarian cancers advanced beyond the earliest stage (localized) involves both cytoreductive surgery and chemotherapy (usually a course of six cycles). Chemotherapy usually consists of a taxane plus carboplatin. The surgery involves a full exploration of the abdomen and maximal removal of the cancer, or “debulking.” The operation can be extensive and may include a total hysterectomy and removal of the ovaries, fallopian tubes, omentum, and sometimes aortic and pelvic lymph nodes. All peritoneal surfaces are scrutinized for evidence of cancer, which is excised if found. To achieve maximal or optimal cytoreduction, the surgery can also include bowel resection, splenectomy, radical pelvic dissection, liver resection, and stripping of the surfaces of the diaphragm and other peritoneal organs and structures. Like any large and long operation with risks of serious complications, this surgery is best performed at an institution that has a high volume of such operations, a full complement of supportive care services, and the availability of other surgical specialists. “Depending on the extent of tumor involvement, we may need a liver surgeon and perhaps a vascular surgeon involved as well,” said Michael M. Frumovitz, M.D., an assistant professor in Gynecologic Oncology. Added Dr. Levenback: “We recommend to the patients we see that they have their surgery here, but they’re often able to have their chemotherapy closer to home if that is desirable.” Dr. Levenback said M. D. Anderson takes an aggressive approach with ovarian cancer surgery, examining and excising tumor deposits from both the lower and upper abdomen. There is good reason to be aggressive: the duration of survival is inversely related to the amount of tumor left behind. Treatment Decisions Traditionally, advanced ovarian cancer is treated first with surgery to debulk the tumor and then with chemotherapy to kill any residual or metastasized cancer cells. However, for some patients, it may be preferable to give part of the chemotherapy before surgery. At M. D. Anderson, the decision is based on two major criteria: the likelihood that the tumor burden can be removed surgically, and the patient’s health and nutritional status. Degree of resectability: Tumor and anatomic factors The preoperative evaluation is therefore an assessment of whether surgery is likely to remove all of the cancer. In patients for whom the likelihood is very high, surgery is a reasonable initial step. But if there is a large tumor load and complete resection appears unlikely, Dr. Frumovitz recommends chemotherapy first. The chemotherapy can reduce the tumor extent, boosting the likelihood that the tumor will be completely removed during surgery. Another anatomic consideration is whether there is disease in very vascular areas where the tumor may not be confined to surfaces—the porta hepatis region behind the liver or in the root of the mesentery, for example. Such findings indicate the cancer is unlikely to be completely resectable, a good reason to consider neoadjuvant therapy. Patient health, nutritional status, and other factors It may seem paradoxical to recommend chemotherapy for a patient considered too weak for surgery. But in practice, such patients benefit the most from preoperative chemotherapy since they often experience a dramatic reduction in tumor load and ascites with a subsequent relief of symptoms after a few chemotherapy cycles. These patients are then able to resume eating and become more comfortable. “The ascites dries up, there is almost always significant tumor shrinkage, and the patients experience a dramatic relief of symptoms,” Dr. Levenback said. “This makes the surgery less radical.” Nutritional status also plays an important role in determining whether to give therapy before or after surgery. According to Dr. Frumovitz, patients with an albumin level less than 2 gm/dL, which suggests a poor nutritional status, have more difficulty recovering from extensive surgery. Dr. Levenback agreed. “If a patient hasn’t been eating or has been vomiting, I pay attention to that as well. Poor nutrition compromises wound healing after surgery,” he said. Thus, patients with a poor nutritional status may benefit from neoadjuvant chemotherapy, which can alleviate symptoms and allow the patient to eat again so her nutritional status can improve before surgery. Other symptoms are also significant in making the case for neoadjuvant chemotherapy. Depression is common, particularly when nutritional status is compromised, and can play an important role in how well patients do postoperatively. “For one thing, depression makes it more difficult to get out of bed and to be active, which slows recovery,” Dr. Levenback said. Mood often improves when the patient experiences relief of other symptoms. According to Dr. Schmeler, another potential benefit of neoadjuvant therapy is that it provides an earlier indication of tumor response to chemotherapy agents. “The most ideal situation is one in which we have a good surgical outcome and chemosensitivity,” she said. Response to chemotherapy can be gauged prior to extensive surgery. “When chemotherapy is given neoadjuvantly and no response is seen, we usually do not proceed to surgery, but rather we change to a different agent,” she said. If patients do not respond to initial chemotherapy agents, their prognosis is very poor and performing surgery will not improve survival. When therapy is given neoadjuvantly, surgery is considered following three cycles of chemotherapy. This allows the tumor burden to decrease prior to cancer cells becoming resistant to the chemotherapy. However, determining when to intervene surgically requires careful monitoring and continual assessment of response, and the plan must be individualized for each patient. Choosing the optimal treatment sequence can be a delicate matter and requires close monitoring of response and collaboration between gynecologic and medical oncologists. Gynecologic oncologists are unique in that they practice both surgical and medical oncology, so they are ideally suited to manage this treatment timing and ensure that care does not become fragmented between subspecialists.
For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789. Other articles in OncoLog, July/August 2009 issue:
Home/Current Issue | Previous Issues | Articles by Topic | Patient Education ©2009 The University of Texas M. D. Anderson Cancer Center |
|||||||||||||||
TOP